Influenza, Human
Conditions
Brief summary
This is a study to assess the immune (antibody) response and safety of the 2013/2014 formulation of Enzira® vaccine in healthy adult volunteers aged 18 years or older.
Interventions
BIOLOGICALEnzira® vaccine
Sponsors
Seqirus
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Males or females aged 18 years or older at the time of vaccination. * Females of child-bearing potential (i.e., ovulating, pre-menopausal, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen for the duration of the study. Females of child-bearing potential must return a negative urine pregnancy test result prior to vaccination with the vaccine.
Exclusion criteria
* Known hypersensitivity to a previous vaccination with influenza vaccine or allergy to eggs, ovalbumin, chicken protein, neomycin, polymyxin, or any components of the vaccine. * Clinical signs of an active infection. * A clinically significant medical condition. * Vaccination with a seasonal or experimental influenza virus vaccine in the 6 months preceding study entry. * Females who are pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | Approximately 21 days after vaccination | As per the criteria specified in the CPMP/BWP/214/96 Note for Guidance on Harmonisation of Requirements for Influenza Vaccines. For haemagglutination inhibition (HI), seroconversion (H1N1, H3N2, and B influenza virus strains) is defined as achieving a post-vaccination titre of ≥ 40 for those participants with a pre-vaccination HI titre of \< 10. A significant increase (H1N1, H3N2, and B influenza virus strains) is defined as a four-fold or greater increase in HI titre for those participants with a pre-vaccination HI titre of ≥ 10. |
| The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | Approximately 21 days after vaccination | GMFI (H1N1, H3N2, and B influenza virus strains) is defined as the geometric mean of the fold increases of post-vaccination antibody titre over the pre-vaccination antibody titre. |
| The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | Approximately 21 days after vaccination | For the H1N1, H3N2 and B influenza virus strains. Note: No SRH data were collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Any Solicited Adverse Events (AEs) | During the 4 days after vaccination (Day 0 plus 3 days) | The percentage of participants reporting any solicited AEs. |
| Frequency of Any Unsolicited AEs | After vaccination until the end of the study; approximately 21 days. | The percentage of participants reporting any unsolicited AEs. Unsolicited AEs include AEs other than those specifically solicited. |
Countries
United Kingdom
Participant flow
Recruitment details
The study was non-randomized with a parallel assignment comprising of 2 groups of healthy volunteers: adults (aged 18 - 59 years) and older adults (aged 60 years or older).
Pre-assignment details
None relevant
Participants by arm
| Arm | Count |
|---|---|
| Adults (18 to 59 Years) Healthy volunteers aged 18 to 59 years received a single 0.5 mL dose of CSL Influenza Vaccine by intramuscular or subcutaneous injection. | 60 |
| Older Adults (60 Years or Older) Healthy volunteers aged 60 years or older received a single 0.5 mL dose of CSL Influenza Vaccine by intramuscular or subcutaneous injection. | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | Adults (18 to 59 Years) | Older Adults (60 Years or Older) | Total |
|---|---|---|---|
| Age, Customized Years | 34.5 years STANDARD_DEVIATION 11.17 | 69.4 years STANDARD_DEVIATION 6.02 | 51.9 years STANDARD_DEVIATION 19.65 |
| Sex: Female, Male Female | 40 Participants | 30 Participants | 70 Participants |
| Sex: Female, Male Male | 20 Participants | 30 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 60 | 16 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination.
GMFI (H1N1, H3N2, and B influenza virus strains) is defined as the geometric mean of the fold increases of post-vaccination antibody titre over the pre-vaccination antibody titre.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population included all participants who were vaccinated with the Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Adults (18 to 59 Years) | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H1N1 strain | 12.90 fold increase | Standard Deviation 4.764 |
| Adults (18 to 59 Years) | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H3N2 strain | 17.85 fold increase | Standard Deviation 5.237 |
| Adults (18 to 59 Years) | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | B strain | 5.30 fold increase | Standard Deviation 3.522 |
| Older Adults (60 Years or Older) | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H1N1 strain | 6.11 fold increase | Standard Deviation 3.675 |
| Older Adults (60 Years or Older) | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H3N2 strain | 5.77 fold increase | Standard Deviation 4.549 |
| Older Adults (60 Years or Older) | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | B strain | 2.81 fold increase | Standard Deviation 2.858 |
Primary
The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2.
For the H1N1, H3N2 and B influenza virus strains. Note: No SRH data were collected.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population included all participants who were vaccinated with the Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults (18 to 59 Years) | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H1N1 strain | 98.3 percentage of participants |
| Adults (18 to 59 Years) | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H3N2 strain | 100 percentage of participants |
| Adults (18 to 59 Years) | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | B strain | 86.4 percentage of participants |
| Older Adults (60 Years or Older) | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H1N1 strain | 95.0 percentage of participants |
| Older Adults (60 Years or Older) | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H3N2 strain | 98.3 percentage of participants |
| Older Adults (60 Years or Older) | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | B strain | 51.7 percentage of participants |
Primary
The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre.
As per the criteria specified in the CPMP/BWP/214/96 Note for Guidance on Harmonisation of Requirements for Influenza Vaccines. For haemagglutination inhibition (HI), seroconversion (H1N1, H3N2, and B influenza virus strains) is defined as achieving a post-vaccination titre of ≥ 40 for those participants with a pre-vaccination HI titre of \< 10. A significant increase (H1N1, H3N2, and B influenza virus strains) is defined as a four-fold or greater increase in HI titre for those participants with a pre-vaccination HI titre of ≥ 10.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population included all participants who were vaccinated with the Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults (18 to 59 Years) | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H3N2 strain | 78.0 percentage of participants |
| Adults (18 to 59 Years) | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | B strain | 54.2 percentage of participants |
| Adults (18 to 59 Years) | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H1N1 strain | 72.9 percentage of participants |
| Older Adults (60 Years or Older) | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H3N2 strain | 55.0 percentage of participants |
| Older Adults (60 Years or Older) | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H1N1 strain | 63.3 percentage of participants |
| Older Adults (60 Years or Older) | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | B strain | 30.0 percentage of participants |
Secondary
Frequency of Any Solicited Adverse Events (AEs)
The percentage of participants reporting any solicited AEs.
Time frame: During the 4 days after vaccination (Day 0 plus 3 days)
Population: The Safety Population included all participants who received the Influenza Vaccine and provided follow-up safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Ecchymosis | 3.3 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Pain | 58.3 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Chills | 10 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Any solicited local AE | 61.7 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Induration > 50 mm | 1.7 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Erythema | 5.0 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Any solicited systemic AE | 25 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Temperature > 38°C for ≥ 24 hours | 0 percentage of participants |
| Adults (18 to 59 Years) | Frequency of Any Solicited Adverse Events (AEs) | Malaise | 23.3 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Temperature > 38°C for ≥ 24 hours | 1.7 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Ecchymosis | 0 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Erythema | 0 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Pain | 13.3 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Chills | 6.7 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Any solicited systemic AE | 10 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Any solicited local AE | 13.3 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Malaise | 6.7 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Solicited Adverse Events (AEs) | Induration > 50 mm | 0 percentage of participants |
Secondary
Frequency of Any Unsolicited AEs
The percentage of participants reporting any unsolicited AEs. Unsolicited AEs include AEs other than those specifically solicited.
Time frame: After vaccination until the end of the study; approximately 21 days.
Population: The Safety Population included all participants who received the Influenza Vaccine and provided follow-up safety data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adults (18 to 59 Years) | Frequency of Any Unsolicited AEs | 46.7 percentage of participants |
| Older Adults (60 Years or Older) | Frequency of Any Unsolicited AEs | 36.7 percentage of participants |